W7: Nociception and Pain - Peripheral and central mechanisms Flashcards
We have sensory receptors that are specialised torespond to changes in both the internal and external environment/ These receptors can be classified according to the type of stimulus that activates them. List and describe some examples
Mechanoreceptors – generate nerve impulses when they, or surrounding tissues are deformed by mechanical stress – touch, pressure (including blood pressure), vibration and stretch (also involved in special senses of hearing and balance)*
Thermoreceptors – sensitive to temperature changes – warm and cold
Photoreceptors – in the retina of the eye –sensitive to light energy
Chemoreceptors – respond to chemicals in solution – control respiratory and cardiovascular function – also involved in our senses of smell and taste
Nociceptors – respond to stimuli that can potentially damage the body’s tissues
Does everyone feel the same sensation and have the same perception of that sensation?
Pain perception varies between individuals
Our survival depends not only on the brain being made aware of changes that are happening (sensation), but also on our conscious interpretation of these events –perception. Receptors recieve same stimulus.
Perception determines how we will respond to stimuli – there may also be a learning component as well
What is the difference between Pain and Nociception?
Pain: cortical awareness
Before cortex = Nociception
The actual signal sent in the nociceptive nerves is known as a nociceptive signal - regarding some noxious stimulation. The nociceptive signal is then interpreted by the brain as a sensation of pain
Pain involves Receptors, Processing in central pathways and Conscious perception. Explain how a stimulus is recieved by the receptor.
A particular type of stimulus (modality) will stimulate a specific sensory receptor – specificity (ex. distinguish between pressure and feel/type)
The energy of the stimulus is converted into a graded electrical response within the receptor = receptor potential, may be excitatory or inhibitory
The stimulus must be within the area that a particular sensory receptor is monitoring – receptive field
Describe ‘generator potentials’
Membrane depolarizations that summate, and may lead to action potentials are referred to as generator potentials
ie. A generator potential must reach threshold in order to generate an action potential through the opening of voltage-gated Na+ ion channels
How is severity of a stimulus distinguished?
Information about the stimulus is encoded in the frequency of the nerve firing – the greater the frequency of firing, the more intense the stimulus
Explain sensory receptor adaptation
Many sensory receptors undergo adaptation –there is a change in their sensitivity (and rate of firing) in response to a constant stimulus –as a result, they respond more to what is new, or what is changing
= PHASIC RECEPTORS
Ex. When sitting you are only aware of the pressure when you sit down or stand up. Not when you are sitting down (no continuous signals)
Describe the difference between tonic and phasic receptors
Phasic receptors: Receptors that rapidly adapt to stimuli – give bursts of impulses at the beginning and the end of a stimulus
Tonic receptors: Receptors that give a sustained response to a stimulus, with little, or no, adaptation Ex. most proprioceptors and nociceptors - normally become more sensitive to noxious stimuli
Explain the sensory pathway of the pressure of holding a pen
Low threshold mechanoreceptor pathway, Primary afferent neurons (sensory neurons) cell body in dorsal root ganglion enter dorsal horn of spinal chord (white matter tracts ie. dorsal columns) -> medulla -> cross over in thalamus -> cerebral/ cortical representation
Explain the processing that happens at the spinal chord level
Information recieved at appropriate level of neuroaxis (vertebral level) through primary sensory nerve (first-order neuron). Processes enter the dorsal horn of the spinal cord.
Some branches of these primary nerves may be involved in local, or spinal, reflexes. Others synapse with second-order sensory nerves associated with the ascending sensory pathways that run to the thalamus.
Third-order neurons, whose cell bodies reside in the thalamus, conduct impulses to the somatosensory cortex
List the three somatosensory pathways (ascending pathways in the spinal cord)
- Non-specific pathways (anterolateral – anterior and lateral spinothalamic tracts
- Specific pathway (medial lemniscal)
- Spinocerebellar tracts
Describe the Spinal Thalamic - anterolateral tract pathway
Non-specific pathway (anterolateral – anterior and lateral spinothalamic tracts)
Noxious information conveyed centrally: pain, temperature and course-touch– sensations we have difficulty in precisely localising –involved in emotional aspects of perception
Desctibe the medial lemniscal dorsal column pathway
Specific pathway - low threshold
mediates precise information from a single type of sensory receptor that can be precisely localised on the body surface – from the thalamus, impulses are relayed to specific areas of the somatosensory cortex
Describe the Spinocerebellar tract pathway
convey information about muscle or tendon stretch, as well as proprioceptive information –these pathways do not contribute to conscious sensation – information used to coordinate skeletal muscle activity
Where does interpretation of sensory information occur? What does this rely on?
Interpretation of sensory information occurs in the cerebral cortex
Relies on where the signal came from, not from the signal itself – one actionpotential is just like another. For example the nature of the nerve that sent the signal tells us what the message is about e.g. pain,touch, warmth, taste etc.
Differs from person to person
What is the major sensory relay station in the brain?
The thalamus
gateway of the cortex - recieved info from all sensory inputs. Sorts edits and packages information for the appropriate area of the sensory cortex
Crude recognition of sensation happens at the thalamus - pleasent or unpleasent
Provide the defintion of pain, distinguishing acute vs chronic
Pain: An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Pain is commonly described as acute/nociceptive/physiological pain, or chronic when it lasts for longer periods.
Chronic Pain as pain without apparent biological value that has persisted beyond the normal tissue healing time (usually taken to be 3 months).
Describe the type of nerve involved in pain
Only sensory (afferent) nerves of clinical interest are those involved in generating sensations of pain – nociceptive nerves
Information regarding pain is transmitted in two types of nerves…Describe.
C-fibres - fine, slow conducting non-myelinated nerves (polymodal nociceptors) - dull, burning pain
Aδ fibres - fine, myelinated fibres - conduct more rapidly, but respond to same stimuli - sharp, well localised pain
Both involved in conveying nociception information centrally
Plus Ax and AB fibres - low threshold mechanoreceptors for proprioception and touch
Explain the biopsychosocial model of health
Pain is multifactorial.
The amount of pain felt in response to a given noxious stimulus varies between individuals* But also varies within an individual – it is particularly dependent on circumstance and mood (subjective sensation)
Desribe the different afferent fibre modalities involved when injury occurs Ex. stubbing a toe
Ad fibre – conduction velocity ~ 20 m/sec – less than 0.1seconds (first pain)
C-fibres – conduction velocity ~ 0.5 m/sec – between 3 and 4 seconds (second pain)
stimulus delivered at same time, difference in perception due to different conduction velocity in the fibres
Primary afferent nociceptive nerves have a peripheral terminal, cell body and central terminal. Describe the significance of this with regards to pathologic conditions.
Peripheral vs central release
CONCEPT OF NEUROGENIC INFLAMMATION - nerve generated/mediated inflammation
Normally The direction of AP’s: stimulus = transduction of info towards CNS (dorsal horn of grey matter) (orthodromic direction) - seen in white picture
BUT
Nothing to stop AP from travelling in either direction when some sort of stimulus initiates ie. toward peripheral terminal (antidromic direction). Glutamate, CGRP ect. release = vasodilation and swelling
= seen in chronic pain conditionsas seen in yellow picture
Happens as there is no difference between peripheral and central terminals
Explain the concept of polymodal nociception and give an example of a polymodal receptor.
Pain may be associated with a whole variety of stimuli- mechanical, chemical, thermal - hence “polymodal nociceptor.” The only common factor is that the stimulus is sufficiently intense to cause tissue damage –hence these nerves normally have a high threshold for stimulation
TRPV1 is a high threshold receptor only located on pain sensing neurons in the periphery (nociceptive N’s). Polymodal receptor activiated by Capsaicin (chemical - chilli), Temperature, H+, Lipids, Mechanical stimuli
potential therapy: TRPV1 antagonists, blocking pain (not motor or autonomic activity)
How is neurogenic inflammation linked to peripheral sensitisation
Glutamate, substance P, CRGP released at the peripheral terminal = vasodilation and increased permeability = infiltration of immune cells/mediators releasing cytokines and signals = change in pH and release of ATP = TRVP1 and acid senscing respond/activate = changes to sensitivity of receptor, more readily excited, easier to activate fibres
Define Hyperalgesia,
Primary and Secondary…
Increased amount of pain associated with a mild noxious stimulus
Primary = Peripheral
Secondary = Central component
Describe the etiology of central sensitisation, the contributing factors and syndromes that result
Compare peripheral and central sensitisation in terms of time and neurons involved
PERIPHERAL:
* Primary afferent
* short term
* Inflammatory or peripheral nerve changes usually at the peripheral ends
* Mechanisms: Post-translational modification, protein upregulation…
Example: heat sensitivity after sunburn.
CENTRAL:
* Second or third order (secondary is medullary dorsal horn for orofacial pain)
* longer term
* Increase in excitability in CNS - may involve protein upregulation, de novo protein expression (not normally produced)…
Recount the endogenous pain suppression systems ie. Desending inhibitory drive
Pathways travelling down the spinal cord from brain…
1. Periaqueductal Gray (midbrain) -> projects to rostral ventral medulla (raphe nuclei) which RELEASES serotonin and projects to dorsal horn
2. Locus Coeruleus releases noradrenaline (acts on Alpha 2 receptors Gi/Go coupled - inhibit adenylate cyclase) and projects to dorsal horn
3. Rostroventral Medulla
Decrease pain transmission from the cord to the brain releasing…
noradrenaline and serotonin and endorphins (enkephalins)
If you can cause pain somewhere, the pathway activated (not specific), therefore pain elsewear is dimished as a result!
Describe “Gate Theory” and how it contributes to pressure anaesthesia
Sometimes C fibre activation = strong activation and excitatory input
BUT If AB fibres activated = activation of inhibitory interneurons = release of GABA = Cl influx = hyperpolarisation of membrane = dimish potenital/response
Describe some adjunct therapies that are used for pain inhibition which are associated with the descending inhibitory pathways
High levels of endophorus opioid peptides and their receptors are found in the PAG, rostral ventral medulla and primarily at the dorsal horn + act locally direclty on peripheral neurons
Part of morphine’s (and other opioid analgesic effects are mediated via these pathways
Define referred pain, why does it occur?
A patient may often feel pain in a part of their body that is quite remote from the tissue that is causing the pain
occurs because there is convergence of the signals from visceral nociceptive nerves with those from the cutaneous nociceptors - within the spinal cord there appears to be mixing of this information
